Format

Send to

Choose Destination
Neuron. 2014 Dec 3;84(5):940-53. doi: 10.1016/j.neuron.2014.10.040. Epub 2014 Nov 20.

NPAS1 represses the generation of specific subtypes of cortical interneurons.

Author information

1
Department of Psychiatry, Neuroscience Program, and the Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, CA 94158-2324, USA. Electronic address: amelia.stanco@ucsf.edu.
2
Department of Psychiatry, Neuroscience Program, and the Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, CA 94158-2324, USA.
3
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143, USA.
4
Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA.
5
Department of Neurological Surgery, Neuroscience Program, University of California, San Francisco, San Francisco, CA 94143, USA.
6
Department of Psychiatry and Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
7
Department of Psychiatry, Neuroscience Program, and the Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, CA 94158-2324, USA. Electronic address: john.rubenstein@ucsf.edu.

Abstract

Little is known about genetic mechanisms that regulate the ratio of cortical excitatory and inhibitory neurons. We show that NPAS1 and NPAS3 transcription factors (TFs) are expressed in progenitor domains of the mouse basal ganglia (subpallium, MGE, and CGE). NPAS1(-/-) mutants had increased proliferation, ERK signaling, and expression of Arx in the MGE and CGE. NPAS1(-/-) mutants also had increased neocortical inhibition (sIPSC and mIPSC) and generated an excess of somatostatin(+) (SST) (MGE-derived) and vasoactive intestinal polypeptide(+) (VIP) (CGE-derived) neocortical interneurons, but had a normal density of parvalbumin(+) (PV) (MGE-derived) interneurons. In contrast, NPAS3(-/-) mutants showed decreased proliferation and ERK signaling in progenitors of the ganglionic eminences and had fewer SST(+) and VIP(+) interneurons. NPAS1 repressed activity of an Arx enhancer, and Arx overexpression resulted in increased proliferation of CGE progenitors. These results provide insights into genetic regulation of cortical interneuron numbers and cortical inhibitory tone.

PMID:
25467980
PMCID:
PMC4258152
DOI:
10.1016/j.neuron.2014.10.040
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center